1. Technical Field
The present invention relates to an oligonucleotide for a detection test of polymorphism of EGFR exon 19 and use thereof.
2. Related Art
An epidermal growth factor receptor (EGFR) is considered to play important roles in lung cancer, and drugs intended to suppress the function of EGFR are used in the field of the treatment of lung cancer. As such drugs, EGFR tyrosine kinase inhibitors such as gefitinib, erlotinib and the like used in the treatment of patients with non-small-cell lung cancer are known, and as for such drugs, an application to adenocarcinoma in addition to the lung cancer is being attempted. However, the effect of the EGFR tyrosine kinase inhibitors may not be obtained sufficiently for a certain range of patients. Another range of patients respond to the EGFR tyrosine kinase inhibitors in the early stages, but the drugs may not become effective beyond expectation gradually.
Therefore, a search of predictive factors to predict the effects of the EGFR tyrosine kinase inhibitors was attempted in order to use the inhibitors, and a mutation of EGFR gene has been found to be an important factor (see, for example, PLoS Medicine, 2005, Vol. 2, No. 3, pp. 225-235; and Journal of Clinical Oncology, 2005, Vol. 23, No. 11, pp. 2513-2520).
As for mutations related to drug sensitivity, for example, a substitution mutation at 790th and 858th in EGFR gene, a deletion mutation at exon 19 in EGFR gene, and the like are known (see, for example, PLoS Medicine, 2005, Vol. 2, No. 3, pp. 225-235; and Journal of Clinical Oncology, 2005, Vol. 23, No. 11, pp. 2513-2520). In particular, as for the deletion mutation at exon 19 in EGFR gene, plural mutant types in which consecutive several bases to ten and several bases are deleted in the above-described exon 19 are known.
On the other hand, in recent years, detections utilizing melting curve analysis (Tm analysis) have been carried out as detection tests for detecting genetic polymorphism. In this method, after amplifying a region including a mutation by PCR method, the melting curve analysis is carried out by using a nucleic acid probe labeled with a fluorescent dye, and the mutation of the base sequence is analyzed based on the results of the melting curve analysis (see, for example, Japanese Patent Application Laid-Open (JA-A) No. 2002-119291).
As for a method of detecting a polymorphism easily and with high sensitivity and high reliability, a method of detecting a polymorphism including using a mutant type primer and a wild type (normal type) primer in the same reaction system to amplify a nucleic acid sequence having a mutant type base preferentially is known (see, for example, WO 2010/001969).